Increased proinsulin secretion, which characterizes type 2 diabetes and insulin resistance, may be due to an intrinsic, primitive defect in proinsulin processing or be secondary to increased demand on b-cells (hyperinsulinemia secondary to insulin resistance). An alternative way to investigate the relation between relative hyperproinsulinemia and increased secretory demand is to study the dynamic changes in the proinsulin-to-insulin ratio after partial pancreatectomy, a model of acute increased b-cell workload on the remaining pancreas. To pursue this aim, patients without diabetes, scheduled for partial pancreatectomy, underwent 4-h mixed-meal tests and hyperinsulinemic-euglycemic clamps before and after surgery. After acute b-cell mass reduction, no changes were observed in the fasting proinsulin-to-insulin ratio, whereas the fold change in the proinsulin-to-insulin ratio significantly increased over time after the meal. Further, our data demonstrate that whole-body insulin resistance is associated with underlying defects in proinsulin secretion, which become detectable only in the presence of increased insulin secretion demand.

Mezza, T., Ferraro, P. M., Sun, V. A., Moffa, S., Cefalo, C. M. A., Quero, G., Cinti, F., Sorice, G. P., Pontecorvi, A., Folli, F., Mari, A., Alfieri, S., Giaccari, A., Increased B-cell workload modulates proinsulin-to-insulin ratio in humans, <<DIABETES>>, 2018; 67 (11): 2389-2396. [doi:10.2337/db18-0279] [http://hdl.handle.net/10807/132115]

Increased B-cell workload modulates proinsulin-to-insulin ratio in humans

Mezza, Teresa;Ferraro, Pietro M.;Moffa, Simona;Cefalo, Chiara M. A.;Quero, Giuseppe;Cinti, Francesca;Pontecorvi, Alfredo;Alfieri, Sergio;Giaccari, Andrea
2018

Abstract

Increased proinsulin secretion, which characterizes type 2 diabetes and insulin resistance, may be due to an intrinsic, primitive defect in proinsulin processing or be secondary to increased demand on b-cells (hyperinsulinemia secondary to insulin resistance). An alternative way to investigate the relation between relative hyperproinsulinemia and increased secretory demand is to study the dynamic changes in the proinsulin-to-insulin ratio after partial pancreatectomy, a model of acute increased b-cell workload on the remaining pancreas. To pursue this aim, patients without diabetes, scheduled for partial pancreatectomy, underwent 4-h mixed-meal tests and hyperinsulinemic-euglycemic clamps before and after surgery. After acute b-cell mass reduction, no changes were observed in the fasting proinsulin-to-insulin ratio, whereas the fold change in the proinsulin-to-insulin ratio significantly increased over time after the meal. Further, our data demonstrate that whole-body insulin resistance is associated with underlying defects in proinsulin secretion, which become detectable only in the presence of increased insulin secretion demand.
2018
Inglese
Mezza, T., Ferraro, P. M., Sun, V. A., Moffa, S., Cefalo, C. M. A., Quero, G., Cinti, F., Sorice, G. P., Pontecorvi, A., Folli, F., Mari, A., Alfieri, S., Giaccari, A., Increased B-cell workload modulates proinsulin-to-insulin ratio in humans, <<DIABETES>>, 2018; 67 (11): 2389-2396. [doi:10.2337/db18-0279] [http://hdl.handle.net/10807/132115]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/132115
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